Cyclophilin C Participates in the US2-Mediated Degradation of Major Histocompatibility Complex Class I Molecules.
Human cytomegalovirus uses a variety of mechanisms to evade immune recognition through major histocompatibility complex class I molecules. One mechanism mediated by the immunoevasin protein US2 causes rapid disposal of newly synthesized class I molecules by the endoplasmic reticulum-associated degra...
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0145458&type=printable |
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| author | Daniel C Chapman Pawel Stocki David B Williams |
| author_facet | Daniel C Chapman Pawel Stocki David B Williams |
| author_sort | Daniel C Chapman |
| collection | DOAJ |
| description | Human cytomegalovirus uses a variety of mechanisms to evade immune recognition through major histocompatibility complex class I molecules. One mechanism mediated by the immunoevasin protein US2 causes rapid disposal of newly synthesized class I molecules by the endoplasmic reticulum-associated degradation pathway. Although several components of this degradation pathway have been identified, there are still questions concerning how US2 targets class I molecules for degradation. In this study we identify cyclophilin C, a peptidyl prolyl isomerase of the endoplasmic reticulum, as a component of US2-mediated immune evasion. Cyclophilin C could be co-isolated with US2 and with the class I molecule HLA-A2. Furthermore, it was required at a particular expression level since depletion or overexpression of cyclophilin C impaired the degradation of class I molecules. To better characterize the involvement of cyclophilin C in class I degradation, we used LC-MS/MS to detect US2-interacting proteins that were influenced by cyclophilin C expression levels. We identified malectin, PDIA6, and TMEM33 as proteins that increased in association with US2 upon cyclophilin C knockdown. In subsequent validation all were shown to play a functional role in US2 degradation of class I molecules. This was specific to US2 rather than general ER-associated degradation since depletion of these proteins did not impede the degradation of a misfolded substrate, the null Hong Kong variant of α1-antitrypsin. |
| format | Article |
| id | doaj-art-c9019b9f06004f24a486fd78f3598ec1 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj-art-c9019b9f06004f24a486fd78f3598ec12025-08-20T03:11:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011012e014545810.1371/journal.pone.0145458Cyclophilin C Participates in the US2-Mediated Degradation of Major Histocompatibility Complex Class I Molecules.Daniel C ChapmanPawel StockiDavid B WilliamsHuman cytomegalovirus uses a variety of mechanisms to evade immune recognition through major histocompatibility complex class I molecules. One mechanism mediated by the immunoevasin protein US2 causes rapid disposal of newly synthesized class I molecules by the endoplasmic reticulum-associated degradation pathway. Although several components of this degradation pathway have been identified, there are still questions concerning how US2 targets class I molecules for degradation. In this study we identify cyclophilin C, a peptidyl prolyl isomerase of the endoplasmic reticulum, as a component of US2-mediated immune evasion. Cyclophilin C could be co-isolated with US2 and with the class I molecule HLA-A2. Furthermore, it was required at a particular expression level since depletion or overexpression of cyclophilin C impaired the degradation of class I molecules. To better characterize the involvement of cyclophilin C in class I degradation, we used LC-MS/MS to detect US2-interacting proteins that were influenced by cyclophilin C expression levels. We identified malectin, PDIA6, and TMEM33 as proteins that increased in association with US2 upon cyclophilin C knockdown. In subsequent validation all were shown to play a functional role in US2 degradation of class I molecules. This was specific to US2 rather than general ER-associated degradation since depletion of these proteins did not impede the degradation of a misfolded substrate, the null Hong Kong variant of α1-antitrypsin.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0145458&type=printable |
| spellingShingle | Daniel C Chapman Pawel Stocki David B Williams Cyclophilin C Participates in the US2-Mediated Degradation of Major Histocompatibility Complex Class I Molecules. PLoS ONE |
| title | Cyclophilin C Participates in the US2-Mediated Degradation of Major Histocompatibility Complex Class I Molecules. |
| title_full | Cyclophilin C Participates in the US2-Mediated Degradation of Major Histocompatibility Complex Class I Molecules. |
| title_fullStr | Cyclophilin C Participates in the US2-Mediated Degradation of Major Histocompatibility Complex Class I Molecules. |
| title_full_unstemmed | Cyclophilin C Participates in the US2-Mediated Degradation of Major Histocompatibility Complex Class I Molecules. |
| title_short | Cyclophilin C Participates in the US2-Mediated Degradation of Major Histocompatibility Complex Class I Molecules. |
| title_sort | cyclophilin c participates in the us2 mediated degradation of major histocompatibility complex class i molecules |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0145458&type=printable |
| work_keys_str_mv | AT danielcchapman cyclophilincparticipatesintheus2mediateddegradationofmajorhistocompatibilitycomplexclassimolecules AT pawelstocki cyclophilincparticipatesintheus2mediateddegradationofmajorhistocompatibilitycomplexclassimolecules AT davidbwilliams cyclophilincparticipatesintheus2mediateddegradationofmajorhistocompatibilitycomplexclassimolecules |